Gynecomastia is the non-cancerous enlargement of male breast tissue, resulting from the growth of the glandular component of the breast. This condition is defined by the presence of a rubbery or firm mass extending concentrically beneath the nipple. While it can occur normally during infancy, adolescence, or older age, it is frequently caused by underlying medical issues or the use of certain medications. Drug-induced cases account for 10% to 25% of all reported instances. Although physically benign, the change in appearance can lead to psychological distress and concerns about body image for many men.
Understanding Drug-Induced Gynecomastia
Medications cause breast enlargement by disrupting the balance between estrogen and androgen. Estrogens stimulate the growth of breast tissue, while androgens, such as testosterone, typically inhibit this growth. Gynecomastia develops when there is an increase in the ratio of estrogen to androgen activity in the body.
A medication can tip this hormonal scale in favor of estrogen through several actions. Some drugs may mimic estrogen’s effects, directly promoting breast tissue proliferation. Other medications can interfere with the body’s natural production of hormones, such as by blocking androgen receptors or inhibiting the synthesis of testosterone. Certain agents can also increase the activity of the enzyme aromatase, which converts androgens into estrogens in peripheral tissues, thereby raising the estrogen-to-androgen ratio.
It is important to differentiate between true gynecomastia and pseudogynecomastia. True gynecomastia involves the proliferation of glandular tissue, which feels rubbery or firm to the touch. Pseudogynecomastia, or lipomastia, is characterized by the accumulation of fatty tissue in the breast area without glandular growth, often seen in overweight individuals. A physical examination is used to make this distinction, as only true gynecomastia is relevant in drug-induced cases.
Key Medication Classes Implicated
Many medication classes are associated with gynecomastia, each acting through one of the hormonal mechanisms described. Hormone-related drugs are a primary category. Anabolic steroids and human chorionic gonadotropin (hCG) can lead to gynecomastia by increasing the substrate available for conversion into estrogen. Antiandrogens, such as bicalutamide and flutamide, used in prostate cancer treatment, directly block the effects of testosterone on breast tissue, removing the inhibitory effect of androgens.
Cardiovascular medications represent another common group of culprits. Spironolactone, an aldosterone antagonist used for blood pressure and heart failure, possesses anti-androgenic and weak estrogen-like properties, frequently leading to dose-dependent gynecomastia. Calcium channel blockers, like verapamil and amlodipine, and the cardiac glycoside digoxin have also been linked to the condition, though their exact mechanism is sometimes less clear.
Psychiatric medications are known to cause breast enlargement, primarily by increasing prolactin levels, a condition called hyperprolactinemia. Certain antipsychotics, including risperidone and haloperidol, block dopamine receptors, which normally inhibit prolactin release, leading to elevated levels of the hormone. Some antidepressant medications, such as fluoxetine and sertraline, have also been implicated through this same mechanism.
A range of gastrointestinal drugs is also known to carry a risk. The H2-receptor antagonist cimetidine, once widely used for ulcers, has a notable anti-androgenic effect that gives it a higher risk compared to newer alternatives. Metoclopramide, a drug used to treat nausea and reflux, can also induce gynecomastia by blocking dopamine and increasing prolactin levels.
Other diverse agents also contribute to drug-induced gynecomastia. The 5-alpha reductase inhibitors, like finasteride and dutasteride, used for prostate enlargement and hair loss, prevent the conversion of testosterone to dihydrotestosterone, which indirectly increases circulating estradiol. Certain chemotherapy drugs, such as alkylating agents and methotrexate, can damage the testicles, causing a reduction in testosterone and a subsequent relative increase in estrogen. Substances like marijuana and phytoestrogens found in some herbal products have also been associated with this condition.
Evaluation and Management
Any man who develops new or painful breast enlargement should seek medical attention to determine the cause. A physician will conduct a thorough physical examination to confirm true glandular enlargement and distinguish it from simple fat deposition. The initial evaluation will also include a detailed review of all current medications and supplements, as drug-induced gynecomastia must be ruled out before considering other, rarer underlying causes.
Blood tests are ordered to check hormone levels, which may include testosterone, estradiol, luteinizing hormone (LH), and prolactin. These tests help to exclude other medical conditions that can cause a hormonal imbalance, such as liver disease, kidney failure, or thyroid issues. Imaging, like a mammogram, is reserved for cases that are unilateral, feel suspicious, or do not clearly resolve, to rule out the possibility of breast cancer.
The management of drug-induced gynecomastia begins with addressing the causative agent. If the medication is suspected, the first action is to discontinue the drug or switch to an alternative, but this must be done under the supervision of a healthcare provider. In many instances, the gynecomastia will spontaneously resolve within six months to a year after stopping the offending medication.
If the causative medication cannot be stopped or the condition persists, pharmacological treatment may be considered, especially for painful cases. Anti-estrogen medications, such as tamoxifen, may be used to block the effects of estrogen on the breast tissue, particularly if the condition is caught in its early, proliferative phase. For long-standing gynecomastia that has persisted for over a year, fibrosis may set in, making medical therapy less effective. In these chronic or highly symptomatic cases, surgical options like reduction mammoplasty may be necessary to remove the persistent glandular tissue.